Phagocytosis and fluid transport in the retinal pigment epithelium (RPE) are necessary for visual processing and survival of the photoreceptors. The long-term goal of this proposed study is to understand the molecular regulation of these processes. The applicant has identified a novel G protein- coupled receptor, epithelium neuropeptide receptor (ENPR). Its sequence is most closely related to neuropeptide receptors, especially that for neuropeptide Y. Transcripts encoding ENPR are present in the RPE and ciliary body; they are not present in other tissues, with the exception of the brain. This restricted pattern of expression suggests that ENPR controls a unique G protein-coupled pathway important to the specialized functions of the RPE. The applicant proposes to perform functional characterization of the novel receptor ENPR in order to the test the hypothesis that ligand activation regulates RPE phagocytosis and fluid transport. These studies will include structural characterization of the human gene, analysis of cellular and subcellular localization, identification of the native ligand, G-protein partners, and second messengers. The elucidation of ENPR receptor function and signaling pathways may allow better understanding of how ENPR activation is translated into physiological responses of the RPE required for normal functioning of the photoreceptors.